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Dev Cell. 2011 Mar 15;20(3):364-75. doi: 10.1016/j.devcel.2011.01.005.

MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.

Author information

1
Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, 411-8540, Japan. toshiaki.watanabe@yale.edu

Abstract

MITOPLD is a member of the phospholipase D superfamily proteins conserved among diverse species. Zucchini (Zuc), the Drosophila homolog of MITOPLD, has been implicated in primary biogenesis of Piwi-interacting RNAs (piRNAs). By contrast, MITOPLD has been shown to hydrolyze cardiolipin in the outer membrane of mitochondria to generate phosphatidic acid, which is a signaling molecule. To assess whether the mammalian MITOPLD is involved in piRNA biogenesis, we generated Mitopld mutant mice. The mice display meiotic arrest during spermatogenesis, demethylation and derepression of retrotransposons, and defects in primary piRNA biogenesis. Furthermore, in mutant germ cells, mitochondria and the components of the nuage, a perinuclear structure involved in piRNA biogenesis/function, are mislocalized to regions around the centrosome, suggesting that MITOPLD may be involved in microtubule-dependent localization of mitochondria and these proteins. Our results indicate a conserved role for MITOPLD/Zuc in the piRNA pathway and link mitochondrial membrane metabolism/signaling to small RNA biogenesis.

PMID:
21397847
PMCID:
PMC3062204
DOI:
10.1016/j.devcel.2011.01.005
[Indexed for MEDLINE]
Free PMC Article

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